The initial section of this proposal deals with a physico-chemical study of Clq wherein the molecule would be characterized by sedimentation co-efficients, intrinsic viscosities, solvent perturbation difference spectroscopy and hydrogen exchange under conditions known to affect this macromolecule. Objectives of these experiments are to determine the molecular basis for some unusual aspects of Clq which are: (1) thermal and acid instability, (2) ionic strength, divalent cation and chelating agent effects, (3) the role collagen-like structures might have, and (4) the numbers, locations and structural role of aromatic residues in Clq as they might relate to the above. These studies would lay the groundwork for extensive hydrogen exchange experiments of Clq interacting with monomeric lgG, wherein the exchange characteristics of each reacting component, under a variety of conditions would be determined. From these the following would be determined and/or attempted: (5) role of conformational change, if any, upon binding for either component, (6) valence of Clg and binding affinity of these complexes, and (7) nature, i.e. size and structure, of binding site on each molecule. The role of aromatic residues at the binding surfaces would also be determined from spectroscopy. In related experiments where Clq interactions would be studied with antigen reacted antibody, a search would be made for conformational changes in Clq. Conditions would be varied in these studies to include: (8) Clq interacting with antigen-antibody complexes of various size and composition, (9) Clq interacting with antigen complexed antibody reacting at one combining site, and (10) an identical system but with antibody reacted at both combining sites. These experiments would be used to determine the role of aggregation of lgG in Clq binding relative to possible conformational changes in lgG as they might relate to binding. Having completed these phases, studies would be done in attempts to determine physical mechanisms within Cl leading to its activation. These would initially involve recombination studies of Cl subcomponents and culminate with Cls hydrogen exchange parameters as they might be affected by reaction of Cl with antigen-antibody complexes.